VARIATIONS IN CRANIOFACIAL AND VELOPHARYNGEAL STRUCTURES AMONG INDIVIDUALS WITH 22Q11.2 DELETION SYNDROME by Lakshmi Kollara Sunil July, 2016 Director of Dissertation: Jamie Perry, PhD Major Department: Communication Sciences and Disorders 22q11.2 deletion syndrome is the most common genetic cause of velopharyngeal dysfunction. Studies examining 22q11.2 deletion syndrome have thus far primarily focused on variations in the bony framework. Limited information exists regarding the velopharyngeal muscle variations for this clinically challenging population. However, with advances in MRI, muscle and soft tissue imaging is possible. A series of experiments were thus designed to explore and validate the use of our research methodology on normal control participants and a single participant with 22q11.2 deletion syndrome, before initiating the study on a larger sample of children with 22q11.2 deletion syndrome. The overarching aims of this investigation were to examine craniofacial and velopharyngeal characteristics among children with 22q11.2 deletion syndrome and to determine whether craniofacial measures can predict velopharyngeal structure and muscle configurations in this population. This investigation represents the first large scale attempt to image children with 22q11.2 DS without sedation. The aim of Study I was to validate the use of a supine MRI scanner over an upright scanner to obtain data of interest. Study II was focused on the application of a child-friendly MRI protocol to ensure data collection on young pediatric participants without the use of sedation. The aim of Study III was to translate our child-friendly MRI scanning protocol to a clinical population and assess feasibility in a single participant with 22q11.2 deletion syndrome. Study IV assessed craniofacial and velopharyngeal characteristics among children with 22q11.2 deletion syndrome using the imaging protocol detailed in studies one, two, and three. Results from this study suggest that children with 22q11.2 deletion syndrome have several craniofacial and velopharyngeal characteristics that are significantly different compared to children with normal velopharyngeal anatomy. This investigation describes a safe and effective method to obtain MRI data in a clinically complex population without the use of sedation. Individuals with 22q11.2 deletion syndrome present with unique velopharyngeal muscle variations that may contribute to the high rate of velopharyngeal dysfunction associated with this syndrome. VARIATIONS IN CRANIOFACIAL AND VELOPHARYNGEAL STRUCTURES AMONG INDIVIDUALS WITH 22Q11.2 DELETION SYNDROME A Dissertation Presented to the Faculty of the Department of Communication Sciences and Disorders East Carolina University In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in Communication Sciences and Disorders by Lakshmi Kollara Sunil July, 2016 © Lakshmi Kollara Sunil, 2016 VARIATIONS IN CRANIOFACIAL AND VELOPHARYNGEAL STRUCTURES AMONG INDIVIDUALS WITH 22Q11.2 DELETION SYNDROME by Lakshmi Kollara Sunil APPROVED BY: DIRECTOR OF DISSERTATION: _______________________________________________________ Jamie Perry, PhD COMMITTEE MEMBER: _________________________________________________ Heather Harris Wright, PhD COMMITTEE MEMBER: _________________________________________________ Charles Ellis, Jr, PhD COMMITTEE MEMBER: _________________________________________________ Xiangming Fang, PhD COMMITTEE MEMBER: _________________________________________________ Adriane Baylis, PhD CHAIR OF THE DEPARTMENT OF COMMUNICATION SCIENCES AND DISORDERS: __________________________ Jamie Perry, PhD DEAN OF THE GRADUATE SCHOOL: ___________________________________________________ Paul J. Gemperline, PhD To my loving family ACKNOWLEDGEMENTS My deepest gratitude and appreciation to my mentor Dr. Jamie Perry for inspiring me to pursue my PhD. I can never thank you enough for the guidance, support, and friendship that you have provided me. Thank you for nurturing my passion for cleft palate research and for the wisdom and humor you have shared along the way. Thank you also for always having faith in me and for encouraging me to pursue my ideas. I am so honored to have had the opportunity to work under your guidance and direction and to be your first PhD graduate. I would like to thank my committee members, Dr. Heather Wright, Dr. Charles Ellis, Dr. Xiangming Fang, and Dr. Adriane Baylis for the collaboration, guidance, and thought provoking suggestions that each of them offered to me over the years. A huge thank you to all the faculty at East Carolina University for their encouragement and support throughout my graduate degrees. Dr. Heather Wright, I am so thankful for your insights, advice, and encouragement. My thanks to Dr. Balaji Rangarathnam for his helpful guidance on international paperwork. Dr. Joseph Kalinowski, thank you for sharing your perspectives on research and life in academia. A special thank you to Dr. Kathleen Cox and Ms. Lori Kincannon for helping me juggle two graduate degrees and an intense clinical practicum. I would like to thank Mr. Jason Conrad in the Office for Research Integrity and Compliance for his expertise on all IRB related matters. I would also like to thank my research collaborators Dr. Adriane Baylis, Dr. Richard Kirschner, Dr. Gregory Bates, Mr. Mark Smith, and Ms. Alyssa Martz at Nationwide Children’s Hospital for their expertise and contributions to this study. My thanks also to all the families and children who enthusiastically participated in my studies. I would like to thank the Cleft Palate- Craniofacial Journal and the Journal of Speech, Language, and Hearing Research for permission to include copyrighted articles. My thanks also to the Cleft Palate Foundation and the American Cleft Palate-Craniofacial Association for funding two of my research studies. To my friends Graham, Stephen, Hannia, Courtney, Larrin, Hannah, and Udayasree, life in Greenville would have been very hard to survive without you all. Thank you for helping me celebrate my accomplishments and for being there for me during some tough times. Graham, I am so thankful for your friendship, moral support, technical guidance, and coffee breaks during our time together in the program. Stephen, Hannia and Ian, thank you for being my family here the past four years. Thank you to my grandparents Yeshoda Ramunni and Kausalya Chathunny for your words of wisdom and blessings. To my uncle Chandroth and aunt Sarasa, thank you for welcoming me into the United States with open arms and for always being there for me. Vandhu, thank you for being my rock. Amma and Acha, I am so appreciative of all the sacrifices you made to get me to where I am today. I can never thank you enough for the unconditional love, constant support, and motivation you have provided me my entire life. Thank you for all that you do for me, no matter how far apart we may be. TABLE OF CONTENTS LIST OF TABLES ........................................................................................................... xiii LIST OF FIGURES ...........................................................................................................xv CHAPTER 1: INTRODUCTION ........................................................................................1 Study I ......................................................................................................................2 Study II.....................................................................................................................3 Study III ...................................................................................................................4 Study IV ...................................................................................................................5 References ................................................................................................................6 CHAPTER 2: LITERATURE REVIEW .............................................................................7 History of 22q11.2 DS .............................................................................................7 General Overview of Characteristics .......................................................................7 Craniofacial Features ...................................................................................9 Platybasia .....................................................................................................9 Cranial Length ...........................................................................................11 Cervical Spine ............................................................................................13 Oral Cavity .................................................................................................13 Velopharyngeal Anatomy and Physiology in 22q11.2 DS ....................................14 Pharyngeal Anatomy ..................................................................................14 Palatal Anomalies ......................................................................................16 Asymmetry of the Palate and Pharynx in 22q11.2 DS1 ............................18 Speech Characteristics ...........................................................................................19 Speech Surgery and Outcomes ..............................................................................20 MRI Investigations of the Velopharynx in 22q11.2 DS ........................................22 References ..............................................................................................................24